Currently, many biological response modifiers (BRM) have been identified. Examples include interleukins and cytokines. The thymus also plays an important role in the overall immunomodulation. One could say that the thymus is the brain of the immune system. The thymus is considered to have a key function in the development and function of the immune system and the biological defense mechanisms against cancer and chronically infected cells.
Thymic tissue is responsible for selected transformation of precursor cells into different T-cells: i.e., helper (CD4+) T-lymphocytes, which aid in the differentiation of other lymphocytes; killer cells (NK cells); cytotoxic cells; and suppressor (cytotoxic) (CD8+) T-lymphocytes (1-3) Having been released into the bloodstream, intestinal and peripheral tissues, the lymphocytes are characterized by well-defined antigens or activation markers on their surface. Their activities are extra-thymic.
There is a delicate interaction between the thymus and the active bone marrow. There is a direct and positive correlation between hypo-function of the thymus and the decline of production of colony-stimulating factors (CSF). Therefore, in cases where there is insufficient production of CSF, the therapeutic application of thymus peptides can be helpful.
Chronic hepatitis B (CHB), HIV, chronic hepatitis C (CHC) and malaria are chronic diseases from which tens of million of people currently suffer without any cure. The cellular branch of immunity is responsible for vigilance against these chronic viruses, fungi, yeast, and parasitic infections as well as against neoplasms and the symptoms of aging. Thymus extracts have been used clinically in a variety of ways involving some of these conditions. They have been used orally and as injectables, by themselves and in combination with other therapeutics. Thymus extracts have been used to treat severe and chronic allergies involving the respiratory tract and skin as well as in severe acute and chronic infectious diseases. The extracts have also been shown to reduce post-surgical infections and decrease the damage of chemotherapy and radiation, and have also been used as adjuncts to mainstream therapy for treatment of neoplasm. All of these conditions have been treated successfully with thymus extracts from bovine.
In a randomized study in patients with malignant melanoma, thymus peptides caused an increased tumor-free period, a longer survival time and increased quality of life (4). In another randomized study in intermediate- and high-grade non-Hodgkins lymphoma, patients were treated with thymus peptides in addition to standard chemotherapy. The treated patients tolerated thymus peptides quite well and had a significantly higher complete response rate than those patients who did not receive thymus peptides (5). In a further randomized study in patients undergoing colorectal surgery showed that the patients who received thymus peptides in addition to Cefotetan did significantly better in lowering the rate of abdominal abscesses and upper respiratory tract infections (6). A randomized study performed in women with advanced breast cancer documented that the women who received thymus peptides in addition to their chemotherapy regimen tolerated the chemotherapy significantly better and had a reduced rate of secondary infections (7,8).
In line with the above findings, its appears that thymus peptides can be used for enhancing bone marrow function and protecting the patient against myelo-suppression of standard chemotherapy; for supporting bone marrow recovery after radiation and chemotherapy; for preventing secondary infections due to immunosuppression caused by standard chemotherapy and surgical interventions; for increasing the complete and partial response rate to anticancer therapies; and for improving lymphocyte function and biological defense mechanisms.
The immune system is composed of many different cells, including T-cells, B-cells, NK-cells, etc. The origin of these different cells varies. Premature T-cells originate in the bone marrow and later on move to the thymus. Different processes take place in the thymus that lead to the production of mature T-cells and to the secretion of various peptides that control the immune response. The T-cells can be divided into several sub-groups, e.g., T-helper cells, T-cytotoxic cells, T-memory cells and T-regulatory cells. Each subset has its own function during the immune response. These sub-groups are characterized by the different antigens presented on their membranes. For example, T-helper cells present the CD4 antigen on their membrane, while T-cytotoxic cells present the CD8 antigen on their membrane.
CD4+ T-cell play a regulatory and are believed to be linked to peripheral self tolerance. The existence of thymus-derived regulatory T-cells was initially suggested by the onset of autoimmune diseases in mice after thymectomy on day 3 of life. These disorders were found to be due to loss of peripheral CD4+ T-cells that constitutively express IL-2R alpha (CD25), which appears late in the periphery after birth. Physiologically generated CD4+CD25+cells inhibit a wide range of autoimmune and inflammatory disorders, e.g. colitis.
Despite numerous studies, the mechanism by which CD4+CD25+ T-cells exert their regulatory function is unclear. Some studies have shown that regulation in vivo is dependent on the production of suppressive cytokines such as IL-10 and TGF-β and cell-surface molecules such as CTLA-4. In vivo studies have shown that the suppressive effect is not mediated by cytokiaes but rather by cell contact.
CD8+ T-cells have been reported to be essential in vivo to prevent experimental autoimmune encephalomyelitis and to participate in oral tolerance. Regulatory CD8+CD28-T-cells can be generated and expanded in vitro by multiple rounds of stimulations by allogenic APC's but it is not known whether this population exists in vivo. A new study revealed a new regulatory population of CD8+ cells which also constitutively expresses CD25 and which possesses very similar characteristics to CD4+CD25+ cells.
These cells produced IL-10, Foxp3, and CTLA-4 and inhibit CD25-T-cell response to anti-CD3 stimulation through cell contacts with efficiency similar to CD4+CD25+.
It is believed that these 2 subpopulations of cells, CD4+CD25+ and CD8+CD25+, participate in the regulation of the irnmune response.